Thirteenth World Conference

The Lives to Come

Pier Giuseppe Pelicci

Dr. Pier Giuseppe Pelicci is Chairman of the Department of Experimental Oncology (DEO) at the European Institute of Oncology, Milan (Italy), Scientific Director of the SEMM Foundation (European School of Molecular Medicine, Milan, Italy) and President of the Cogentech Consortium. IEO is a comprehensive cancer center focused on advanced treatments, diagnostics, clinical trials, cancer prevention, training, higher education and advanced research. SEMM is private foundation whose mission is to foster innovative education in molecular medicine, medical nanotechnology and bio-ethics. Cogentech is a Consortium owned by IEO and IFOM whose mission is the development of biomedical technological platforms for genomic research and Molecular Medicine programs. At IEO, Pelicci is responsible for the strategic planning of the IEO institute research programs, including basic, translational (Molecular Medicine Program) and clinical research. At SEMM, Pelicci is responsible for the development of three PhD programs (Molecular Medicine, Medical Nanotechnology, Life sciences: foundationsÃ°ics) Dr. Pelicci is member of the American Association for Cancer Research, the European Molecular Biology Organization, the European Haematology Association, the European Society for Engineering and Medicine, the European Cytokine Society, The New York Academy of Sciences, the American Society for Microbiology, the Italian Association of Biophysics and Molecular Biology, the Italian Society of Cancerology. He is past president (1998-2000) of the Italian Society of Experimental Hematology. Dr. Pelicci was honored with several prestigious international fellowships and awards, such as the "C. Cioffrese" Prize for Cancer Research (Fondazione Carlo Erba, Italy), the “Foundation Chiara d'Onofrio”Â (Italy), the “Guido Venosta”Â Prize of the Italian Foundation for Cancer Research, the Award for “Excellence in Medicine”Â of the American-Italian Foundation for Cancer Research (New York, US), the H. S. Raffaele Prize (Italy). He is presently Full Professor of Pathology at the University of Milan and cofounder of the Biotech holding Genextra. Genextra controls four Biotech companies (Congenia, DAC, Tethis and Intercept). Dr.Pelicci is co-founder and co-director of the IFOM-IEO Campus, a research infrastructure that host IFOM, the IEO laboratory research activities, SEMM, Genextra and Cogentech.

Longevity Genomics.

Research on aging and, more specifically, on the molecular mechanisms governing life-span duration is relatively new. Yet, it has made extraordinary progress over the past 30 years.

The first breakthrough that paved the way for a new era in aging research came with the discovery of the existence of genes whose inactivation determines an increase in the maximum life span of an individual. These genes (few dozen in all) were discovered in both invertebrates (Drosophila and C. elegans) and mammals. Since their absence determines the prolongation of life, these genes are called aging genes (genes, that is, whose activity accelerates aging). The study of their physiological function has allowed their classification in three groups: i) genes that enhance the activities of insulin, a hormone that regulates cell metabolism; ii) genes that increase the accumulation of oxidative stress in the tissue; iii) genes that regulate the elongation of chromosome ends, and, thus, proliferative potential in stem cells. The existence of aging genes it is not easy to reconcile in evolutionary terms, as it is not immediately clear how genes that do not increase fitness can be selected.
A second major step forward was due to the discovery of the existence of genes whose activities prolong life (longevity genes). In particular, it is thanks to these genes if organisms are able to prolong life when subjected to calorie restricted diets (caloric restriction effect). Although detailed investigations have just begun, these genes too appear functionally connected to the regulation of cell metabolism.
Recent studies suggest that aging genes, longevity genes and caloric restriction all act on the same animal function: the capacity of an organism to adapt to the environment under conditions of nutrient deprivation. Undoubtedly, one of the big evolutionary challenges was represented by the alternation of cycles of food availability.
Finally, a third step forward came with the discovery that life extension by manipulation of aging genes or caloric restriction associates with a greater resistance to the incidence and the severity typical of aging-associated diseases (such as cancer or cardiovascular diseases). Although intuitively obvious, this suggests that the mechanisms behind the process of aging and aging- associated diseases overlap (for example, oxidative stress, insulin resistance, etc.). Applicatively, therefore, the study of the molecular mechanisms associated with aging can provide new molecular targets for the design of drugs against aging-associated diseases.
This possibility is quickly becoming very concrete. Indeed, there are at least two examples where the treatment of mice with drugs directed against the products of aging or longevity genes, respectively, has had an effect on life span or on some aspects of the aging-associated diseases. All these data, while preliminary, tell us that the study of the mechanisms regulating the duration of life may have a significant impact on aging, healthy aging or aging-associated diseases. It is likely that this knowledge will have a further acceleration in the near future. We expect further acceleration of this knowledge in the near future from studies of environmental modifications, in particular of diet, on chromatin (the complex of DNA and proteins around it). These aspects will be discussed.